Biology subjects
Publications and source records attributed to Miguel Beato.
HiC-inspector is a toolkit for the analysis and visualization of data generated by high-throughput chromatin conformation capture (HiC). The analysis module comprises steps of data formatting, genome alignment, quality control and filtering, identification of genome-wide chromatin interactions, and statistics. The interactive browser enables visual inspection of interaction data generated and analysis results.
Highlights- Hormonal gene regulation requires synthesis of PAR and its degradation to ADP-ribose by PARG\n- ADP-ribose is converted to ATP in the cell nuclei by hormone-activated NUDIX5/NUDT5\n- Blocking nuclear ATP formation precludes hormone-induced chromatin remodeling, gene regulation and cell proliferation\n\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=165 HEIGHT=200 SRC=\"FIGDIR/small/006593v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (46K):\norg.highwire.dtl.DTLVardef@e2c9fborg.highwire.dtl.DTLVardef@13ab596org.highwire.dtl.DTLVardef@16799d7org.highwire.dtl.DTLVardef@a53086_HPS_FORMAT_FIGEXP M_FIG C_FIG SummaryKey nuclear processes in eukaryotes including DNA replication or repair and gene regulation require extensive chromatin remodeling catalyzed by energy consuming enzymes. How the energetic demands of such processes are ensured in response to rapid stimuli remains unclear. We have analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly-ADP-ribose to ADP-ribose. Nuclear ATP synthesis requires the combined enzymatic activities of PARP1, PARG and NUDIX5/NUDT5. Although initiated via mitochondrial derived ATP, the nuclear source of ATP is essential for hormone induced chromatin remodeling, gene regulation and cell proliferation and may also participate in DNA repair. This novel pathway reveals exciting avenues of research for drug development.
The human genome is segmented into Topologically Associating Domains (TADs), but the role of this conserved organization during transient changes in gene expression is not known. Here we described the distribution of Progestin-induced chromatin modifications and changes in transcriptional activity over TADs in T47D breast cancer cells. Using ChIP-Seq, Hi-C and 3D modelling techniques, we found that the borders of the [~]2,000 TADs in these cells are largely maintained after hormone treatment but that some TADs operate as discrete regulatory units in which the majority of the genes are either transcriptionally activated or repressed upon hormone stimulus. The epigenetic signatures of the TADs are coordinately modified by hormone in correlation with the transcriptional changes. Hormone-induced changes in gene activity and chromatin remodeling are accompanied by differential structural changes for activated and repressed TADs. In response to hormone activated TADs exhibit higher density of internal contacts, while repressed TADs show less intra-TAD contacts. Integrative 3D modelling revealed that TADs structurally expanded if activated and compacted when repressed, and that this is accompanied by differential changes in their global accessibility. We thus propose that TADs function as \"regulons\" to enable spatially proximal genes to be coordinately transcribed in response to hormones.